Did You Know? Phosphate Binders

Aug 25, 2021

Serum Phosphate

Serum phosphate concentration is primarily determined by the ability of the kidneys to excrete dietary phosphate. In kidney disease, excretion can be impaired, leading to higher phosphate levels. Hyperphosphatemia has been associated with increased morbidity and mortality. Phosphate binders are used to treat hyperphosphatemia that stems from many different causes including hyperparathyroidism, bisphosphonates, vitamin D toxicity, and very commonly, kidney disease.1 Acute hyperphosphatemia typically resolves in 6-12 hours if kidney function is sufficient, and the phosphate excretion can be increased with saline infusion.2 Dietary phosphate restriction and phosphate binders are utilized to treat chronic hyperphosphatemia found in chronic kidney disease. In most patients, the goal is to maintain the serum phosphate concentration between 3.5 and 5.5 mg/dL. Phosphate binders work exactly as they sound- they attach to phosphate from food in the digestive tract, ultimately decreasing the amount of phosphate absorbed. 3 For this reason, phosphate binders should ALWAYS BE TAKEN WITH MEALS to be effective. Phosphate binders are classified as calcium-containing or non-calcium

Phosphate binders are classified as calcium containing or non-calcium containing.  Typically, the non-calcium containing binders are preferred unless the serum calcium is low:

  • Low calcium:  Use a calcium-based binder such as Phoslo (more $) or Tums (Less $).
  • Normal-high: Use a non-calcium-based binder.  1st line:  Sevelamer carbonate (Renvela) or Lanthanum carbonate (Fosrenol—chewable form).

Phosphate Binders4

Calcium-BasedCalcium-BasedCalcium and Metal FreeCalcium and Metal FreeMetal-BasedMetal-Based
Calcium Carbonate (Tums)Calcium Acetate
(PhosLo, Phoslyra)
Sevelamer Carbonate
(Renvela)
Sevelamer Carbonate
(Renvela)
Lanthanum Carbonate
(Fosrenol)
Aluminum Hydroxide (Amphojel)
Content (mineral/metal/element)Contains 40% elemental Ca2+ (200 mg elemental Ca2+ per 500 mg CaCO3)Contains 25% elemental Ca2+ (169 mg elemental Ca2+ per 667 mg cap)NoneNoneContains 250, 500, 750, or 1000 mg elemental lanthanum per tabletContains 250, 500, 750, or 1000 mg elemental lanthanum per tablet
FormsLiquid, tablet, chewable, capsule, gumCapsule, tabletTablet, powderTabletTablet, chewableLiquid
Tablet
Capsule
DosingOFF label use6
Not to exceed 2 grams/day
667mg/tab
2 tablets with each meal
Inc. every 2-3 weeks up to 3-4 tablets with each meal7
Initial: (serum phosphorus)
5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times daily
≥7.5 mg/dL to <9 mg/dL: 1,200 to 1,600 mg 3 times daily
≥9 mg/dL: 1,600 mg 3 times daily
Maintenance dose: adjustment based on serum phosphorous concentration
(goal range of 3.5 to 5.5 mg/dL)
Inc. dose by 400-800mg per meal at 2-week intervals8
Initial: (serum phosphorus)
5.5 mg/dL to <7.5 mg/dL: 800 mg 3 times daily
≥7.5 mg/dL to <9 mg/dL: 1,200 to 1,600 mg 3 times daily
≥9 mg/dL: 1,600 mg 3 times daily
Maintenance dose: adjustment based on serum phosphorous concentration
(goal range of 3.5 to 5.5 mg/dL)
Inc. dose by 400-800mg per meal at 2-week intervals8
Available 500mg, 750mg, 1000mg
1500mg divided with meals
Inc. every 2-3 weeks up to 3000mg daily9
OFF label use10
For short-term use (≤4 weeks) in patients with severe hyperphosphatemia (eg, >7 mg/dL) despite other treatment
Side EffectsHeadache, hypercalcemia, hypophosphatemia, abdominal pain, anorexia, constipation, flatulenceHypercalcemia, diarrhea, nausea, vomitingMetabolic acidosis, diarrhea, dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, peritonitisMetabolic acidosis, diarrhea, dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, peritonitisDiarrhea, nausea, vomiting, hypocalcemia, abdominal painConstipation, white speckled fecal, fecal impaction, nausea, stomach cramps, vomiting, hypomagnesemia
AdvantagesEffective, inexpensive, readily availableEffective phosphate-binding, potentially for enhanced phosphate-binding capability over calcium carbonate, potentially less calcium absorptionEffective; no calcium/metal; not absorbed; assumed to have similar advantages as sevelamer-HCl; potentially improved acid-base balanceEffective; no calcium/metal; not absorbed; potential for reduced coronary/aortic calcification when compared with calcium-based binders in some studies; reduces plasma concentration of LDL-CEffective; no calcium; chewableVery effective phosphate-binding capacity; variety of forms
DisadvantagesPotential for hypercalcemia-associated risks including extraskeletal calcification and PTH suppression; GI side effectsPotential for hypercalcemia-associated risks including extraskeletal calcification and PTH suppression; more costly than calcium carbonate; GI side effectsCost; may require calcium supplement in the presence of hypocalcemia; GI side effectsCost; potential for decreased bicarbonate levels; may require calcium supplement in presence of hypocalcemia; GI side effectsCost; potential for accumulation of lanthanum due to GI absorption, although long-term clinical consequences unknown; GI side effects, lots of interactionsPotential for aluminum toxicity; altered bone mineralization, dementia; GI side effects

References

  1. “Overview of the causes and treatment of hyperphosphatemia” https://www-uptodate-com.gate.lib.buffalo.edu/contents/overview-of-the-causes-and-treatment-of-hyperphosphatemia?search=phosphate%20binders&source=search_result&selectedTitle=3~133&usage_type=default&display_rank=2
  2. “Overview of the causes and treatment of hyperphosphatemia” https://www-uptodate-com.gate.lib.buffalo.edu/contents/overview-of-the-causes-and-treatment-ofhyperphosphatemiasearch=phosphate%20binders&source=search_result&selectedTitle=3~133&usage_type=default&display_rank=2#H16
  3. https://www.ouh.nhs.uk/patient-guide/leaflets/files/62922Pphosphate.pdf
  4. https://www.researchgate.net/figure/Licensed-and-currently-available-oral-phosphate-binders-in-the-US_tbl2_263896133
  5. https://kdigo.org/wp-content/uploads/2017/02/KDIGO-2009-CKD-MBD-Guideline-English.pdf
  6. “Calcium Carbonate” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
  7. “Calcium Acetate” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
  8. “Sevelamer” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
  9. “Lanthanum” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.
  10. “Aluminum Hydroxide” Lexicomp-Drugs Online, Hudson: Lexicomp, Inc.

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Brandi VanValkenburg

Brandi provides personalized care as a pharmacy consultant with HealthDirect's northeastern region.  She has been serving our clients for over 10 years. 

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